Attention-deficit hyperactivity disorder (ADHD) is characterized by inattentiveness and/or hyperactivity and impulsiveness, placing individuals at risk for social, academic, and occupational dysfunction. Pharmacological treatments of ADHD with lowdose administration of amphetamine (AMPH)-Iike stimulants, i.e. methylphenidate, target monoaminergic neurotransmission. Virtually all information regarding actions of AMPH-like stimulants has been obtained using doses that exceed greatly those used clinically. This lack of information concerning the neural actions of therapeutically-relevant doses of methylphenidate and other AMPH-like stimulants represents a substantial lacuna in our understanding of ADHD. ? ? The proposed studies are designed to determine the effects of therapeutically-relevant doses of methylphenidate on: 1) Rates of norepinephrine/dopamine efflux; 2) Basal (tonic) and sensory driven (phasic) discharge of locus coeruleus neurons, and; 3) Cortical and subcortical neuronal circuit function. Ultimately, a better understanding of the neurochemical, cellular and network mechanisms of the therapeutic actions of these drugs is necessary for development of pharmacological treatments that do not possess the negative properties of AMPH-like stimulants. ? ?
|Devilbiss, David M; Waterhouse, Barry D; Berridge, Craig W et al. (2012) Corticotropin-releasing factor acting at the locus coeruleus disrupts thalamic and cortical sensory-evoked responses. Neuropsychopharmacology 37:2020-30|
|Devilbiss, David M; Berridge, Craig W (2008) Cognition-enhancing doses of methylphenidate preferentially increase prefrontal cortex neuronal responsiveness. Biol Psychiatry 64:626-35|